Cell-type-specific and disease-associated expression quantitative trait loci in the human lung.

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors.

Mail-Based Self-Sampling to Complete Colorectal Cancer Screening: Accelerating Colorectal Cancer Screening and Follow-up Through Implementation Science.

Introduction: Leveraging cancer screening tests, such as the fecal immunochemical test (FIT), that allow for self-sampling and postal mail for screening invitations, test delivery, and return can increase participation in colorectal cancer (CRC) screening. The range of approaches that use self-sampling and mail for promoting CRC screening, including use of recommended best practices, has not been widely investigated.

Methods: We characterized self-sampling and mail strategies used for implementing CRC screening across a consortium of 8 National Cancer Institute Cancer Moonshot Initiative Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) research projects.

An integrated cell atlas of the lung in health and disease.

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population.

Cell type-specific and disease-associated eQTL in the human lung.

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis (PF). Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA-sequencing of lung tissue from 67 PF and 49 unaffected donors.

Effect Modification of Selenium Supplementation by Intake and Serum Concentrations of Antioxidants on the Development of Metachronous Colorectal Adenoma.

Background: Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se.

Objective: We examined the association between intake and serum concentrations of retinol, β-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin, and α- and γ-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA).

Adaptation of colorectal cancer screening tailored navigation content for American Indian communities and early results using the intervention.

Background: American Indians (AI) experience major colorectal cancer (CRC) screening disparities with commensurate inequity in CRC mortality and other outcomes. The purpose of this report is to describe the methods and early results of adapting a previously successful intervention for the AI community.

Methods: The educational content and delivery strategy of the parent intervention were adapted for AIs guided by an adaptation framework and cultural consultations with the community and clinicians.

A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels.

Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs.

Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent.

Background: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation.

Objectives: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation.

Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyzed the transcriptomes of 605,904 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observed a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs.

Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states.

Longitudinal examination of changing fertility intentions and behaviors over a four-year period in urban Senegal.

Background: Fertility intentions and contraceptive use are often used to demonstrate gaps in programs and policies to meet the contraceptive needs of women and couples. Prior work demonstrated that fertility intentions are fluid and change over a woman's (or couple's) life course with changing marital status, childbearing, and education/employment opportunities. This study uses longitudinal data to better examine the fluidity of women's fertility intentions and disentangle the complex interrelationships between fertility and contraceptive use.

Using a Quality Improvement Approach in the Prevention of Mother-to-Child HIV Transmission Program in Uganda Improves Key Outcomes and Is Sustainable in Demonstration Facilities: Partnership for HIV-Free Survival.

Background: The Partnership for HIV-Free Survival (PHFS) in Uganda used a quality improvement (QI) approach to integrate the prevention of mother-to-child transmission (MTCT) of HIV, maternal and child health, and nutrition services, with the goal of increasing the retention of mother-baby pairs in care and decreasing vertical transmission of HIV.

Methods: This evaluation of PHFS used a retrospective longitudinal design to assess the program's association with 4 outcomes. Data were extracted from patient records from 2011 (before the program) to 2018 (after the program) at 18 demonstration, 18 scale-up, and 24 comparison facilities.

Effects of a Community-to-Clinic Navigation Intervention on Colorectal Cancer Screening Among Underserved People.

Background: Colorectal cancer screening remains suboptimal among poor and underserved people.

Purpose: We tested the effectiveness of a community-to-clinic navigator intervention to guide multicultural, underinsured individuals into primary care clinics to complete colorectal cancer screening.

Methods: This two-phase behavioral intervention study was conducted in Phoenix, Arizona (2012-2018).

On the sustainability of a family planning program in Nigeria when funding ends.

Few studies have examined the sustainability of family planning program outcomes in the post-program period. This article presents the results of a natural experiment where the Nigerian Urban Reproductive Health Initiative Phase I programming ended in early 2015 and Phase II activities continued in a subset of cities. Using data collected in 2015 and 2017, we compare contraceptive ideation and modern family planning use in two cities: Ilorin where program activities concluded in 2015 and Kaduna where program activities continued.

Assessing the sustainability of the Nigerian urban reproductive health initiative facility-level programming: longitudinal analysis of service quality.

Background: To date, there is little information on the sustainability of family planning (FP) service quality after completion of a donor-funded program. This paper examines the sustainability of the Nigerian Urban Reproductive Health Initiative (NURHI) program on quality of FP services in two cities: Ilorin, where the program ended in March 2015 and Kaduna where the program continued.

Methods: Data come from three time periods: 2011, before program implementation; 2014, near Phase 1 completion; and 2017, two-years post Phase 1.

DNA methylation among firefighters.

Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip.

Selenium supplementation and insulin resistance in a randomized, clinical trial.

Objective: While controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.

Research Design And Methods: In a subset of 400 individuals participating in a randomized, placebo-controlled trial of Se at 200 µg/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention.

Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development.

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203).

Selenium and Type 2 Diabetes: Systematic Review.

Several studies have investigated the potential role of selenium (Se) in the development of type 2 diabetes (T2D) with disparate findings. We conducted a systematic review and meta-analysis to synthesize the evidence of any association between Se and T2D. PubMed, Embase, and Scopus were searched following the Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA).

Adherence to Nutrition and Physical Activity Cancer Prevention Guidelines and Development of Colorectal Adenoma.

Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber ( = 503) and Ursodeoxycholic Acid ( = 854) trials were performed.

Is increased colorectal screening effective in preventing distant disease?

Background: Screening in the average risk population for colorectal cancer (CRC) is expected to reduce the incidence of distant (i.e., metastatic) CRCs at least as much as less advanced CRCs.